Two Opposite Signal Transducing Mechanisms Regulate a G-Protein-Coupled Guanylyl Cyclase

Two Guanylylcyclases Regulate the Muscarinic Activation of Airway Smooth Muscle

“…Given that CNP specifically activates GC-B receptors and that it activates GC-A receptors only marginally, the significant CNP effect on TSM cGMP production indicates that NPR-GC-B is the most abundantly expressed tracheal membrane-spanning GC isoform, further confirming the RT-PCR results in [37]. This NPR-GC-B is regulated in an opposite way by two MAChRs signaling cascades, acting the M2AChR as an inhibitor and the M3AChRs as an activator of this NPR-GC-B as mentioned in [55].…”

“…Thus, ASMC from Control and OVA-exposed rats were cultured and exposed to these NPR-GC-B activators. Thus, in Figure 11, the total GC activity at OVA-ASMC was stimulated by CNP, ANP and muscarinic agonist (Cch) indicating that NPR-GC-B was present in Control ASMC, which are similar results described in intact BTSM strips and isolated plasma membranes from BTSM in references [37,38,53,55]. In addition, the OVA-ASMC showed a more significant stimulation by these NPR-GC activators.…”

“…This 60-s cGMP signal is a product of NPR-GC-B as above mentioned in references [35,54,55]. Recently, we further recognized that muscarinic agonist and mastoparan activations of NPR-GC-B in isolated BTSM plasma membranes fraction involve this mastoparan-sensitiveGq16 protein in [54].…”

“…Recently, it has been suggested that a plasma membrane-bound GC, may provide a localized pool of cGMP in [68], which seems to be in a similar trend suggested by our work. The second signal peak is a product of a the activation of M3AChR coupled to the stimulation of mastoparan-sensitive Gq16 as reported in reference [54] to turn on a transmembrane-homodimer as NPR-GC-B as described in [35,55].…”

G Protein-coupled Endothelial Receptor for Atypical Cannabinoid Ligands Modulates a Ca2+-dependent K+ Current

“…Together, these data suggest that the novel, G i /G o -coupled receptor activated by abn-cbd is positively coupled to guanylyl cyclase to raise intracellular cGMP, which activates protein kinase G. Both cGMP and protein kinase G have been shown to modulate Ca 2ϩ -dependent K ϩ channels (17,40), and phosphorylation of the Ca 2ϩ sensor on the channel by protein kinase G may result in its increased sensitivity to voltage and/or Ca 2ϩ and hence an increased K ϩ current. There is precedent for the activation of guanylyl cyclase by a G i /G o -coupled receptor; in tracheal smooth muscle, muscarinic M 2 receptors couple to guanylyl cyclase through a G i /G o -dependent mechanism (41).…”